Mucinous tumors are classified into benign cystadenoma/cystadenofibroma/adenofibroma, MBT/atypical proliferative mucinous tumor (APMT), and mucinous carcinoma. Mucinous tumors are characterized by cyst and glands lined by epithelial cells containing intracytoplasmic mucin. They tend to be the largest of all ovarian tumors, with many of them being 15–30 cm in diameter and are typically unilateral. Approximately 75% are benign, 10% are borderline, and 15% are carcinomas. In the review of 166 frozen diagnosis of mucinous tumors, 67.5% were benign, 22.3% were borderline, and 10.2% were malignant.

Serous tumors are classified as benign cystadenoma/cystadenofibroma/adenofibroma, serous borderline tumor (SBT)/atypical proliferative serous tumor (APST), SBT/APST micropapillary variant/noninvasive low-grade serous carcinoma (LGSC), invasive LGSC, and high-grade serous carcinoma (HGSC). Approximately 70% of serous tumors are benign, 10% are borderline, and 20% are carcinomas. However, among 120 serous tumors on FS, borderline and malignant tumors accounted for 22.5% and 43.3%, respectively, and benign tumors comprised only 24.2%.

Endometrioid tumors include benign endometriotic cyst and cystadenoma/adenofibroma, endometrioid borderline tumor (EBT)/atypical proliferative tumor (APET), and malignant carcinoma. In the review of 43 frozen diagnoses, endometriotic cysts accounted for 70%, malignant tumors accounted for 25%, and borderline tumors accounted for 5.0%.

Benign tumors are exceptionally rare, and borderline tumors account for <1%. Most tumors are clear cell carcinomas. Clear cell tumors arise as a solid adenofibromatous or a cystic endometriotic type [19,20]. In the solid type, the cut surface is sponge-like with numerous small cysts (Fig. 9A). A benign tumor is microscopically characterized by benign-appearing glandular epithelium, whereas a borderline tumor shows atypical or malignant epithelium without invasion or microinvasion. A frankly invasive component (>5 mm in size) is present in a malignant tumor. A cystic tumor is unilocular or multilocular, with protruding polypoid masses in the lumens (Fig. 9B). The lining of the cyst represents benign or atypical endometriosis. The tumors are characterized by various cell types and histologic patterns (Fig. 9C). The most diagnostic features include dense hyalinized cores of papillae and hyaline bodies, which are present in 25% of the cases (Fig. 9D). Because a benign or borderline clear cell tumor is exceedingly rare, multiple additional sections should be taken to rule out carcinoma. Marked nuclear atypia is helpful in the differentiation of intracystic papillary clear cell carcinoma from SBT/APST. The distinction from primary ovarian HGSC and EC as well as the distinction between metastatic clear cell carcinoma and Mullerian clear cell carcinoma are not crucial on FS. Yolk sac tumor and dysgerminoma should be ruled out, because fertility-sparing surgery is an option for young patients. Germ cell tumors typically occur in younger age groups (2^nd and 3^rd decades) than clear cell carcinoma. All 11 clear cell carcinomas diagnosed on FS were correct; however, 3 tumors were diagnosed as adenocarcinoma and 1 as mucinous carcinoma. The other 1 case arising in association with endometriosis was misdiagnosed as endometriosis.

Seromucinous tumor is a mixed epithelial neoplasm with 2 or more Mullerian cell types, all accounting for at least 10% of the epithelium. The tumors are unilocular or paucilocular with papillary excrescences (Fig. 10A). Seromucinous tumors are associated with endometriosis in 30% of the cases (Fig. 10B) [4]. The most predominant epithelial cell types are serous and endocervical-type mucinous epithelium (Fig. 10C). The tumors are classified into benign seromucinous cystadenoma/adenofibroma, borderline seromucinous tumor/atypical proliferative seromucinous tumor, and malignant seromucinous carcinoma. Benign and malignant tumors are rather uncommon, and most tumors belong to the borderline category. These tumors are architecturally similar to SBT/APST, but larger papillae have edematous stroma containing neutrophils (Fig. 10D). Microinvasion, intraepithelial carcinoma, and a micropapillary pattern may occur.

On FS, the distinction from SBT/APST may be difficult; however, it is not important at the time of FS.

Seromucinous tumors were frequently diagnosed as serous tumors, but also as mucinous or endometrioid tumors in this review.

Fibroma is the most common type of stromal tumor. The tumor is solid, firm, white or tan, or hemorrhagic because of torsion (Fig. 11A). Microscopically, the tumor is composed of intersecting bundles and fascicles of spindle cells with hyalinization, collagen bands, or plaque (Fig. 11B). Cellular fibroma accounts for about 10% and is densely cellular with scant collagen. The number of mitosis is ≤3/10 HPFs, and nuclear atypia is absent or mild. A cellular tumor with mitotic activity of ≥4/10 HPFs and no more than mild nuclear atypia is defined as mitotically active cellular fibroma, whereas a tumor with at least moderate nuclear atypia and increased mitotic activity of ≥4/10 HPFs, often with atypical form, is termed as fibrosarcoma [21].

Thecomas are relatively uncommon tumors that typically occur in postmenopausal women with symptoms of estrogen production. The tumors are unilateral, and the cut surface is solid and yellow. The tumor is microscopically composed of sheets of oval or round cells with moderate to abundant pale eosinophilic cytoplasm. The tumor is designated as a fibrothecoma when an area resembling a fibroma is present.

On FS, the distinction of fibroma from thecoma is not important. However, the distinction from metastatic carcinoma with reactive stromal proliferation (Krukenberg tumor) is important. Bilaterality should raise a suspicion for metastasis, and careful microscopic examination to search for scattered tumor cells with a signet ring or breast lobular carcinoma should be done. Thorough sampling is recommended when minor sex cord elements are present, to rule out GCT or SLCT. Luteinized cells in thecomas may suggest the possibility of Leydig cell tumor or SLCT. Distinction from Leydig cell tumor is not crucial, but identification of a Sertoli cell component is important because surgical staging is required for SLCT [22].

Among 30 tumors, 1 fibrothecoma was suggested to be a metastatic poorly differentiated carcinoma and 3 cellular fibromas were diagnosed on permanent section.

GCT is a low-grade malignant tumor composed of granulosa cells often with a variable number of fibroblasts and theca cells. The tumors comprise of two different clinicopathologic subtypes: adult and juvenile. The adult type more often occurs in postmenopausal patients, whereas the juvenile type mainly occurs in children and younger women. The patients may present abnormal vaginal bleeding associated with estrogenic manifestations. Patients with adult GCT have concurrent endometrial hyperplasia (25%) or adenocarcinoma (5%), and younger patients may present isosexual precocity [23]. The tumors are commonly unilateral, typically solid and cystic, and tan-yellow or white. Microscopically, the adult form is characterized by a mixture of various morphologic patterns, and the tumor cells are uniform with scanty cytoplasm and pale grooved nuclei (Figs. 12A, 12B). The juvenile form typically shows macrofollicles filled with basophilic secretions, as well as cells with moderate to abundant cytoplasm and darker nuclei usually without grooves [24].

The surgical treatment of GCT in postmenopausal patients includes total hysterectomy and bilateral SO as part of the complete surgical staging procedure, whereas fertility-sparing surgery including unilateral SO and staging procedure may be done in younger patients with unilateral tumor without surface involvement [25,26].

On FS, the distinction between the adult and juvenile forms is not crucial. The distinction of the adult type from benign sex cord-stromal tumors and metastatic carcinoma is the most important, because these lesions do not require surgical staging. Clinical history, bilaterality, and marked nuclear atypia with numerous mitotic figures should raise suspicion for a metastatic carcinoma. An adult-type tumor with a microfollicular pattern can mimic a metastatic or primary typical or atypical carcinoid tumor. Carcinoid tumors have round nuclei with smooth nuclear membrane and stippled chromatin, in contrast to oval nuclei and nuclear groove in GCT (Figs. 12C, 12D). In the distinction of the sarcomatoid type from cellular fibroma/fibrosarcoma, the characteristic nuclear features and identification of other morphologic patterns of GCT can be helpful. If the frozen diagnosis is adult GCT, evaluation of the endometrium is also recommended.

One SLCT and 1 metastatic atypical carcinoid were diagnosed as adult GCT on FS.

SLCT is a rare tumor that commonly occurs in young patients and presents androgenic symptoms. Most of the tumors are unilateral, solid, and tan-yellow, or partly cystic in tumors with a retiform pattern or a mucinous heterologous component. Microscopically, the tumor is characterized by open or solid tubules, cords and diffuse sheets of primitive stromal appearance of Sertoli cells, and a variable degree of Leydig cells (Fig. 13A). The tumors are classified into well, moderately, and poorly differentiated groups, according to the differentiation of Sertoli cells. Approximately 20% of the tumors have heterologous components such as mucinous epithelium, cartilage, or skeletal muscle, and approximately 15% of SLCTs show a retiform pattern [4,27]. The prognosis of patients depends on the differentiation and on the presence of retiform and heterologous components [28]. Conservative fertility-sparing surgery in young patients with stage 1 tumor includes unilateral SO and staging procedure; however, bilateral SO, total hysterectomy, and complete surgical staging are performed in patients who do not wish to preserve fertility [22].

The differential diagnosis between moderately and poorly differentiated SLCT and adult GCT is not easy on FS, but the surgical management is basically similar (Fig. 13B). In distinguishing from ovarian primary sertoliform EC, the presence of unilaterality, younger age, absence of squamous differentiation, and presence of Leydig cells can be helpful in the diagnosis of SLCT. Surgical staging is more extensive in ovarian epithelial malignancy. Among 2 SLCTs, 1 tumor was diagnosed as adult GCT on FS.

Teratoma is a very common ovarian tumor. Mature teratomas account for >95% of all teratoma and most commonly occur during the reproductive ages. On the other hand, immature teratomas are relatively rare, representing 1–3% of all teratomas, and most commonly occur during the first 2 decades of life. Bilaterality is observed in 10–15% of the cases. Mature teratoma is almost always cystic, but rarely solid. Immature teratoma is solid and cystic. Microscopically, the neural elements in mature teratoma may mimic the primitive immature neuroepithelial tissue of immature teratoma [29]. Immature mesenchymal and endodermal elements are sometimes difficult to detect on FS. The diagnosis of immature teratoma should rely on the identification of immature neuroepithelial tissue (Fig. 14A). Carcinosarcoma, composed of carcinomatous and sarcomatous components, may be considered in the differential diagnosis, but it most often occurs in the postmenopausal ages (Fig. 14B). Monodermal teratomas include struma ovarii and carcinoid tumor. Malignant transformation of mature teratoma rarely occurs, most often in postmenopausal patients; however, when it occurs, full surgical staging is required [30]. The FS diagnosis of mature cystic teratoma is straightforward, but adequate sampling from solid areas including the Rokitansky protuberance should be done.

Dysgerminoma is the most common malignant germ cell tumor, occurring most often during the 2^nd and 3^rd decades of life. It is a rapidly growing tumor and may arise in dysgenetic gonads with gonadoblastoma. The tumor is unilateral in 80–90% of the cases, and is large, solid, and flesh and tan-yellow in color (Fig. 15A). Microscopically, the tumor is characterized by solid nests, sheets, or cords of relatively uniform polygonal cells with abundant clear or eosinophilic cytoplasm and prominent nucleoli, with intersecting fibrous septae infiltrated with lymphocytes (Fig. 15B).

On FS, contralateral ovarian biopsy should be performed to rule out bilateral tumor or underlying dysgenetic gonads and/or gonadoblastoma, for which bilateral oophorectomy is indicated. However, fertility-sparing surgery (unilateral SO with peritoneal biopsy and lymph node sampling) is adequate for unilateral dysgerminoma [31]. The distinction from other malignant germ cell tumors, yolk sac tumor and embryonal carcinoma is not crucial on FS. The surgical management is essentially identical. The most important issue concerning dysgerminoma on FS is its differentiation from diffuse large cell lymphoma, because the management of lymphoma is basically nonsurgical (Figs. 15C, 15D).

One of 2 dysgerminomas was diagnosed as metastatic carcinoma, whereas 1 malignant lymphoma was interpreted as dysgerminoma on FS in this review.

Yolk sac tumor accounts for 20% of malignant germ cell tumors and occurs during the 2^nd and 3^rd decades of life. This tumor may be a component of a mixed germ cell tumor and rarely occurs in association with a surface epithelial tumor, usually endometrioid [32,33]. The serum alpha-fetoprotein level is elevated. The tumor is nearly always unilateral, large, solid, and tan-yellow, with areas of necrosis, hemorrhage, and cyst formation. Microscopically, various growth patterns, such as reticular pattern, endodermal sinus pattern with Schiller-Duval bodies, solid pattern, alveolar glandular pattern, and other rare polyvesicular vitelline or hepatoid patterns, are present within the same tumor (Fig. 16).

The distinction from other malignant germ cell tumors is not crucial on FS, because the surgical management is similar. The most important entity in the differential diagnosis is clear cell carcinoma, which requires more extensive staging. Clear cell carcinoma usually occurs in older ages and is commonly associated with endometriosis.

Choriocarcinoma is a rare type of malignant germ cell tumor. Nongestational choriocarcinoma occurs in children and young adults and may be mixed with other malignant germ cell tumor components, whereas gestational choriocarcinoma occurs in older age groups. Elevated serum beta-human chorionic gonadotropin level and isosexual pseudoprecocity may be present. The tumor is typically large and solid and cystic, often with hemorrhage and necrosis. Microscopically, a biphasic pattern of cytotrophoblasts and multinucleated syncytiotrophoblasts is typically present (Fig. 17). Other malignant germ cell tumors may show isolated syncytiotrophoblastic giant cells, but the distinction on FS is not crucial. However, poorly differentiated surface epithelial carcinoma with trophoblastic differentiation, typically occurring in postmenopausal patients, should be differentiated because it requires more aggressive surgery [34]. One choriocarcinoma in this review was interpreted as torsion because of the presence of extensive hemorrhagic necrosis.

Metastatic adenocarcinoma from the colorectum is often bilateral and solid or solid and cystic with a tan-yellow or gray cut surface (Fig. 18A). Ovarian surface involvement and multinodular growth pattern are commonly seen. Histologically, the tumor shows variable-sized, often cystic, irregular glands. A cribriform architecture with dirty necrosis is called a garland pattern. The differential diagnosis from primary ovarian mucinous and endometrioid adenocarcinoma is important (Fig. 18B). Bilaterality, size <10 cm, ovarian surface involvement, and a multinodular growth pattern suggest metastasis rather than a primary ovarian tumor [37]. If the tumor shows mucinous differentiation, intraoperative surgical evaluation of the abdominal cavity is recommended to find the possible primary lesion of the metastasis. Squamous differentiation in adenocarcinoma indicates primary ovarian EC rather than metastasis from a primary colorectal tumor.

The primary site of metastatic signet ring cell carcinoma is most commonly the stomach (70%), but less commonly the colorectum, appendix, breast, and pancreaticobiliary system [38,39]. The tumor is bilateral, grossly solid, and tan-yellow or white, but may also be firm or soft, and gelatinous (Fig. 19A). Histologically, the tumor shows a pseudo-lobular pattern with hypercellular and hypocellular areas or diffusely cellular dense stroma (Fig. 19B). Signet ring cells individually infiltrate or form small clusters or tubules. Extracellular mucin may be present. On FS, signet ring cells may be missed and misinterpreted as fibroma or fibrothecoma. Primary ovarian sex cord-stromal tumors are usually unilateral.

The most common appendiceal tumor with ovarian involvement is low-grade mucinous neoplasm. Less commonly, intestinal-type adenocarcinoma, signet ring cell carcinoma, and goblet cell carcinoid tumor may involve the ovary. Low-grade mucinous neoplasm is often associated with pseudomyxoma peritonei and is frequently bilateral, but shows predominantly right-sided involvement among unilateral cases [40]. The cut surface reveals a multilocular cyst with tan-gray, mucoid appearance and surface involvement. The appendix is dilated with mucus. Histologically, the cysts are lined by flat or undulating mucinous epithelium with spillage of mucin into the stroma (pseudomyxoma ovarii). Goblet cells may be present. The mitotic activity is not significant. The presence of pseudomyxoma peritonei, bilaterality, and ovarian surface involvement indicate appendiceal metastasis rather than primary ovarian tumor [41]. However, similar morphologic features may be present in a primary mucinous tumor associated with a mature teratoma (Fig. 20). Appendectomy and FS evaluation of the appendix should be done even in the absence of gross abnormalities.

Uterine cervical adenocarcinoma and, less commonly, squamous cell carcinoma may spread to the ovary, even in cases in which the primary tumor is small and clinically unsuspected for ovarian metastasis. Histologically, the tumors may mimic primary borderline or malignant mucinous and endometrioid tumors [42]. Endometrial and ovarian involvement by endometrioid or serous carcinoma may represent a synchronous independent primary tumor or ovarian metastasis from a primary endometrial tumor. The distinction between these possibilities is impossible at the time of FS and is usually not crucial for the intraoperative surgical management.